Many interrelated factors such social environment, education, life style/behaviors, social status, and biology influence health and well being (Lillie-Blanton M and LaViest T 1996). Health disparities present among minorities, the poor and the medically underserved are likely due the dysfunctional interaction of these factors. There are well-documented differences in health status among groups defined by age, race, ethnicity, and socioeconomic status. Throughout the industrialized world, studies of national and international cohorts have shown an inverse relationship between SES and rates of disease and death (Goldman N. 2001). In addition over the past decade, evidence from cross-sectional studies and nationally representative follow-ups suggests that there are persistent disparities among African-Americans and other minority groups compared to whites in morbidity and mortality. While socioeconomic status is believed to be a significant influence on health disparities among minorities, it has also been noted that differences in health status may remain even when socioeconomic status and health care access is equalized (Williams 1999, 1997, Marmot 2001). Therefore, it is necessary to consider race and socioeconomic status as separate variables that are not equivalent. The need to understand the driving factors behind persistent black-white health disparities in overall longevity, cardiovascular disease, and cerebrovascular disease, has led to the development of the NIA IRP Healthy Aging in Neighborhood of Diversity across the Life Span (HANDLS) Program, a community-based research effort designed to focus on evaluating health disparities in socioeconomically diverse African-Americans and whites in Baltimore. This study is unique because it is a multidisciplinary project that will not only assess physical parameters but also evaluate genetic, demographic, psychosocial and psychophysiological parameters over a 20-year period. It will also employ novel research tools, mobile medical research vehicles to improve participation rates and retention among non-traditional research participants. Recently, we completed a pilot study called Healthy Aging in Nationally Diverse Longitudinal Samples (HANDLS) in a largely African-American, low socioeconomic neighborhood that recruited a sample of convenience with 442 participants nearly 40% of whom were men. Our experience with the pilot study has revised our previously held beliefs about barriers to participation through our efforts to connect with community groups and our presence in the neighborhood in our mobile medical research vehicle. Although the goal of the pilot was to assess the feasibility of the study and o develop the necessary logistics for operating a community-based mobile medical research vehicle, we also succeeded in collecting data on some aspects of health disparities. Preliminary analyses of our psychophysiological data suggests important differences in blood pressure responses to certain stimuli among African American subjects that may be tied to differences in control of mechanisms of blood pressure. These analyses support the notion that there is a delay in cardiovascular recovery among African Americans that may be a potential factor in the cardiovascular health disparity between Blacks and Whites. In addition, there was a significant association between symptoms of depression and cardiovascular reactivity, and in women, a significant association between loneliness and peripheral resistance. These results serve to highlight the multiple levels of system functioning that may contribute to health disparities in cardiovascular disease, especially hypertension. Compared with published data from the Baltimore Longitudinal Study of Aging, carotid artery intimal-medial thickness (IMT) is higher in African Americans than Whites. Further evaluation of possible confounding variables shows that the higher IMT in our younger, low socioeconomic status, African American cohort does not appear to be due to differences in blood pressure, tobacco use, or body mass index. The pilot data from analysis of muscle strength via KinKOM also suggests that the pilot cohort was weaker than age-matched African Americans in the Baltimore Longitudinal Study of Aging. The pilot sample had much higher levels of depressive symptomatology as measured by the CESD suggesting greater rates of depression or that this widely used instrument is less accurate for screening in low socioeconomic and minority cohorts. Preliminary results indicate that there are significant age differences in depressive symptoms in women but not in men, a surprising result because there is no evidence for age differences in depressive symptoms in nationally representative data. In addition, there were no mean differences between women and men, particularly surprising because nationally representative data unanimously shows that women self-report more depressive symptoms than men. The HANDLS study will be a multidisciplinary, prospective epidemiologic longitudinal study examining the influence and/or interaction of race and socioeconomic status on the development of cardiovascular and cerebrovascular health disparities among minority and lower socioeconomic status subgroups. The study plans to recruit a representative sample of whites and African Americans between 30 and 64 years old from twelve census tracts in Baltimore City in both low and high socioeconomic strata as a fixed cohort following the overall design. By collecting a baseline assessment and 5 follow-up triennenial assessments over approximately 20 years, there will be sufficient power (>.80) with 30 participants per group (race by SES by sex by age group) remaining after 20 years. There will also be sufficient power (>.80) to compare rates of change among groups after the baseline assessment. Anticipating attrition due to non-response, morbidity, and mortality yields an initial sample of approximately 4,000 participants or about 335 participants per tract. The initial examination and recruitment phase will take approximately 3 years to complete. The study data will be collected in two parts. The first part of participant examination is a household interview that will include questionnaires about health status, health services, psychosocial factors, nutrition, neighborhood characteristics, and demographics. The second part of the examination data will be collected on the medical research vehicles; these include medical history and physical examination, dietary recall, cognitive evaluation, psychophysiology assessments including heart rate variability, arterial thickness, carotid ultrasonography, assessments of muscle strength and bone density, and laboratory measurements (blood chemistries, hematology, biomaterials for genetic studies). The primary objective of HANDLS is to create a new longitudinal study on minority health focused on investigating the differential influences of race and socioeconomic status on health in an urban population. Specifically, HANDLS will to investigate the longitudinal effects of socioeconomic status and race on the development of cerebrovascular disease and cardiovascular disease; changes in psychophysiology, cognitive performance, strength and physical functioning, health services utilization, and nutrition, and their influences on one another and on the development of cardiovascular and cerebrovascular disease. Selecting a cohort that spans ages 30-64 at baseline enhances the opportunities to gain insights into minority aging and the development of age-related disease over the planned 20 years of this study.